סמינר המחלקה להנדסה ביו-רפואית
Immunological responses against glycosylated biotherapeutics and biodevices in humans
1Departments of Cell Research & Immunology, Tel Aviv University, Tel Aviv, Israel
Susceptibility to structural valve deterioration is one of the major drawbacks of bioprosthetic heart valves (BHVs). N-glycolylneuraminic acid (Neu5Gc) is an immunogenic dietary-carbohydrate antigen in humans because of inactivation of the gene encoding CMP-N-acetylneuraminic acid hydroxylase (CMAH), and all humans have circulating anti-Neu5Gc antibodies. We hypothesized that interaction of anti-Neu5Gc antibodies with Neu5Gc on BHVs could lead to immune response resulting in valve deterioration through calcification. We demonstrate Neu5Gc in both native calcified human valves as well as in calcified-BHVs, explanted from human patients, by HPLC and immunohistochemistry. Furthermore, anti-Neu5Gc IgGs were purified from native calcified human valves, validated by a glycan microarray. In the Neu5Gc-free Cmah-KO mouse model, anti-Neu5Gc antibodies promoted calcium deposits in subcutaneous implanted BHV discs, both with passive transfer of affinity-purified human anti-Neu5Gc IgGs, and by active-immunization of Cmah-KO mice with Neu5Gc-containing glyconanoparticles. Thus, co-existence of Neu5Gc/anti-Neu5Gc likely mediate BHV structural valve deterioration.
BSc Biology at TAU
MSc Biochemistry at TAU (Nathan Nelson)
PhD Biochemistry at TAU (Nathan Nelson)
Postdoc University of California San Diego (UCSD; Ajit Varki)
Since 10/2013 started my lab at TAU Faculty of Life Sciences, Dept of Cell Research and Immunology
Vered Padler-Karavani’s research is at the interface of glycobiology, immunology, biotechnology and cancer research and focuses on studying the mechanisms that govern glycan immune recognition and responses in animal models and in humans, both in vitro and in vivo. She is particularly interested in the immunological basis of anti-carbohydrate antibodies and their implications on human diseases and theranostics. Vered received her PhD in biochemistry from Tel Aviv University. She then did her postdoctoral training with Prof. Ajit Varki at UCSD and subsequently moved back to Tel Aviv University where she joined the Department of Cell Research and Immunology in the Faculty of Life Sciences.
Vered Padler-Karavani, Ph.D.
Laboratory of Glycoimmunology
Department of Cell Research and Immunology
The Shmunis School of Biomedicine and Cancer Research
The George S. Wise Faculty of Life Sciences
Center for Nanoscience and Nanotechnology
Tel Aviv University
Tel Aviv 69978 Israel
l Responses Against Glycosylated Biotherapeutics and Biodevices in Humans ד"ר ורד פדלר-קראווני הפקולטה למדעי החיים, אוניברסיטת תל אביב